3j93
Fitting of Fab into the cryoEM density map of EV71 procapsid in complex with Fab22A12
Structural highlights
Publication Abstract from PubMedEnterovirus 71 (EV71) is responsible for seasonal outbreaks of hand, foot, and mouth disease in the Asia-Pacific region. The virus has the capability of causing severe disease and death, especially in young children. Although several vaccines are currently in clinical trials no vaccines or therapeutics have been approved for use. Previous structural studies have revealed that two antigenically distinct capsid forms are produced in EV71 infected cells: an expanded empty capsid, sometimes called procapsid, and the infectious virus. Specifically an immunodominant epitope of EV71 that maps to the virus canyon is structurally different between the procapsid and virus. This structure function study shows that the procapsid can sequester antibodies thus enhancing EV71 infection in vitro. The results presented here suggest that due to conformational differences between the EV71 procapsid and virus, the presence of the procapsid in natural virus infections should be considered in the future design of vaccines or therapeutics. IMPORTANCE: In a picornavirus infection both an infectious and a non-infectious empty capsid, sometimes referred to as procapsid, are produced. It was novel to discover that the procapsid form of enterovirus 71 (EV71) was expanded and antigenically distinct from the infectious virus. Previously it had been supposed that this empty capsid was an off pathway dead end, or at best served as storage of pentameric subunits, which was later shown to be unlikely. It remains unexplained why picornaviruses evolutionarily conserve the wasteful production of so much non-infectious capsid. Here we demonstrate that the EV71 procapsid has different antigenic properties than the infectious virus. Thus the procapsid has the capacity to sequester neutralizing antibody and protect the virus, promoting or restoring a successful infection in vitro. This important observation should be considered in the future design and development of vaccines and therapeutics. The Enterovirus 71 procapsid binds neutralizing antibodies and rescues virus infection in vitro.,Shingler KL, Cifuente JO, Ashley RE, Makhov AM, Conway JF, Hafenstein S J Virol. 2014 Nov 26. pii: JVI.03098-14. PMID:25428877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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